Stimulation of tumour growth by wound-derived growth factors
Stimulation of tumour growth by wound-derived growth factors
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DOI：
10.1038/sj.bjc.6690223
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发表时间：
1999-03-01
影响因子：
8.8
通讯作者：
Neeman, M
中科院分区：
文献类型：
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作者：
Abramovitch, R;Marikovsky, M;Neeman, M
这项工作的目的是确定磁共振成像（MRI）研究的分子基础，该研究表明，在猪身上注射皮肤损伤的伤口液可以减少裸鼠植入的C6胶质瘤球体的血管化和开始生长的滞后，并加速肿瘤加倍的时间。前者的作用可归因于伤口液的血管生成能力，通过MRI在体内检测，并在体外促进内皮细胞增殖。后一种效应，即诱导肿瘤生长的速度，与伤口液的血管生成活性以及伤口液直接对肿瘤细胞产生有丝分裂的发现一致，并加速了球形培养中C6胶质瘤的生长。在伤口液中存在的多种生长因子中，两个关键因子，肝素结合表皮生长因子（EGF）样生长因子（hbv -EGF）和血小板衍生生长因子（PDGF），被确定为C6胶质瘤的主要丝裂原，使用特异性中和抗体抑制它们的活性可抑制伤口液对C6胶质瘤DNA合成的丝裂原作用。这项研究表明，损伤对肿瘤进展的刺激作用可能通过针对有限数量的特定生长因子的治疗靶向而减弱。
The goal of this work was to determine the molecular basis for the Magnetic resonance imaging (MRI) studies demonstrated that administration of wound fluid derived from cutaneous injuries in pigs reduced the lag for vascularization and initiation of growth or C6 glioma spheroids, implanted in nude mice, and accelerated tumour doubling time. The former effect can be attributed to the angiogenic capacity of wound fluid as detected in vivo by MRI, and in vitro in promoting endothelial cell proliferation. The latter effect, namely the induced rate of tumour growth, is consistent with the angiogenic activity of wound fluid as well as with the finding that wound fluid was directly mitogenic to the tumour cells, and accelerated growth of C6 glioma in spheroid culture. Of the multiple growth factors present in wound fluid, two key factors, heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) and platelet-derived growth factor (PDGF), were identified as the dominant mitogens for C6 glioma, and inhibition of their activity using specific neutralizing antibodies suppressed the mitogenic effect of wound fluid on DNA synthesis in C6 glioma. This study suggests that the stimulatory effect of injury on tumour progression can possibly be attenuated by therapeutic targeting directed against a limited number of specific growth factors.